Immune system

Immune system

Objectives

• Define immunity • List down the functions of immune system

• Discuss the components of immune response

• Discuss innate and acquire immunity • Describe humeral versus cell mediated immunity

• Discuss Antigen processing ,presentation and recognition

• IMMUNITY: The defense mechanisms of the body against micro-organisms, toxins and other foreign particle which are harmful for the body.

or• Resistance to disease by means of antibodies.

or • The human body capacity to resist almost all type of organism and toxins which tend to damage tissue or organs.

IMMUNE RESPONSE: interaction between antibody & antigen which result in the antigen being eliminated from the body

Function of immune system

• Destroy pathogen• Detect and kill cells such as cancerous cells

• Remove dead cells and other debris from the body

Components of immune system

• Lymphocytes • Neutrophils • Macrophages• Lymphoid tissues ( thymus, spleen, bone marrow, tonsils )

• Immunoglobulin's (antibodies)

Lymphocytes • Lymphocytes are small white blood cells that play a role in the body’s immune response (that is, in the body’s fight against germs and diseases).

• Once they recognize foreign material in the body, they produce chemicals (cytokines) to destroy that material.

• Two types of lymphocyte are produced in the bone marrow.

B lymphocytes (B cells) :- They stay within the bone marrow until they are mature. Once mature, they spread throughout the body and concentrate in the spleen and lymph nodes.

T lymphocytes(T cells):- They leave the bone marrow and mature in the thymus, a gland found in the chest. There are four types of t cell.

Types of t-lymphocytes:

Cytotoxic or killer T cells do their work by releasing lymphotoxins, which cause cell lysis

Cytotoxic T cells, sometimes called killer T cells, destroy tumor cells and cells infected by viruses. They are also called CD8+ (CD8 positive) cells because they have the CD8 protein on their surface membrane.Helper T cells serve as managers, directing the immune response

Suppressor T cells inhibit the production of cytotoxic T cells once they are unneeded, lest they cause more damage than necessary.

Memory T cells are programmed to recognize and respond to a pathogen once it has invaded and been repelled

Activation of Helper T Cells• Cells called phagocytes surround and engulf invaders, a process called phagocytosis.

• Once certain phagocytes have “eaten” a pathogen such as a virus or bacterium, they travel to a lymph node or to the spleen, which are sites where mature T cells assemble.

• The phagocytes digest the pathogen and then send a piece of the pathogen’s body to their cell membrane, where it acts as an antigen

• A phagocyte, which is now known as an antigen-presenting cell, “presents” its newly-acquired antigen to helper T cells.

• A helper T cell with the correct receptor joins to the antigen.

• This begins the process of helper T cell activation.

• The activated T cell releases proteins called cytokines which trigger B cells, cytotoxic T cells and other white blood cells to become active and start attacking the pathogens.

Lymphoid tissue

Antigen:•Antigen is any chemical substance that when introduced into the body is recognized as foreigner.

Characteristics of antigen1.Immunogenicity2.ReactivityImmunogenicity:•The ability to provoke an immune response i.e to stimulate the production of antibodies or proliferation of T cell or both.

Reactivity:The ability of antigen to react specifically with the produced antibodies or cells.

Chemical nature of antigen: Chemically antigen are large complex molecules, most often they are protein such as • nucleoprotein (nucleic acid +protein), • Lipoprotein (Lipid + Protein) • Glycoprotein (carbohydrate + Protein)T cell respond only to antigen that include proteinB cell respond to antigenic proteins, certain lipid carbohydrate and nucleic acid

Complete antigen:• Substance having molecular weight 10000 or more and having both the characteristics of antigen are called complete antigen.

Partial antigen:• Smaller substance which have reactivity but not immunogenicity are called heptens.

• Heptans can stimulate immune response when it binds to larger carrier molecules

Example penicillin may combine with protein and the complex become immuogenic.

Antigenic determinant:• Specific region of antigen molecule which trigger the immune response is called antigenic determinant or epitopes.

• Most antigens have many antigenic determinant each of which induces production of different types of antibodies or T cells

Major histocompatibility complex (MHC):• MHC are the glycoprotein on the surface of cells.

• MHC are also called HLA because it was 1st identified on the surface of WBCs

• There are two categories of MHC antigens Class I and Class II.

• Class I MHC molecules are built into the plasma membrane of all body cell except RBCs.

• Class II MHC molecule appear only on the surface of antigen presenting cell i.e Dendritic cells, macrophages and B cells.

Innate immunity:• The immunity result from general processes directed at specific pathogen is called innate immunity.

It include • Phagocytosis • Destruction of pathogens by acid and other digestive enzymes

• Resistance of skin to invasion of pathogens

• Chemical compound in blood that destroyed pathogens i.e lysozyme, basic polypeptides, complement protein, natural killer cells (lympocytes that kill the tumor and infected cells)

• Innate immunity produce resistance to the diseases like viral such as cholera, cattle plague,

Acquire immunity:• The type of immunity in which the powerfull response against the pathogens like virus ,bacteria and toxin are produced. Acquire immunity is caused by Antibodies and activated lymphocyte.

• Acquire immunity give full protection to the body. For example protection from certain toxin such as paralytic botolinum occur in high dose with immunity but without immunity that dose become lethal .

Types of acquire immunity:• There are two types of acquire immunity

• Cell mediated immunity ( immunity due to cytotoxic T lymphocytes)

• Humeral immunity ( immunity due to antibodies)

• Both types of immunity are initiated by antigens

Cell mediated immunity:• Cellular immunity is directed against intracellular pathogen.

• T cell do not recognize free antigen but do recognize antigen combine with an MHC protein.

• Cytotoxic T cells are activated CD8 cells they attack our own cells if they have become infected by an intracellular pathogen or they have become cancerous.

• Cytotoxic T cells circulated through the body crawling over cells to examine the self antigen on their surface.

• A Cytotoxic T cells knows when some thing is wrong inside the cell because class I MHC protein bring pieces of endogenous protein to the surface of the cell for inspection.

• Only a few kinds of cells have Class II MHC protein these are Antigen Presenting Cell (Dendritic cells, Macrophages and B cells)

• These cells communicate with CD4 cells which are destined to become or have already become helper T cells.

• The antigen that are presented on class II MHC protein are exogenous antigen they originate from out side the cells.

• Steps Pathogen ( Bacteria) ↓ Ingested by Dendritic cell ↓ Intracellularly bacteria is surrounded by phagosome ↓ Phagosome fuse with lysosome ↓ Bacteria is digested into small fragment and the product is presented on the cell surface

Humeral Immunity:• The humoral immune system involves antibodies that are dissolved in extracellular fluids,such as blood plasma, lymph, and mucus secretions known as humors.

• This system uses B cells to produce antibodies that are specifically directed against the antigens.

• The humoral immune response defends mostly against bacteria, bacterial toxins, and viruses in the body’s fluids.

Anti bodies:• Antibodies belong to a class of proteins called

immunoglobulins (Ig). • Another term used with antibodies is antiserum.

• Antiserum is a generic term for fluids containing antibodies.

• The antibody rich serum component is called gamma

globulin. • These proteins can recognize, bind to, and help cause the destruction of antigens. Antibodies can only interact with one antigenic determinant on an antigen.

Structure of Immunoglobulin1.Four (4) polypeptide chains: • 2 identical LIGHT chains and 2 identical HEAVY chains.

2.Both light and heavy chains are • held together by COVALENT DISULFIDE BONDS.

3.Heavy chains are interconnected by DISULFIDE LINKAGES in the HINGE region.

4.Ig has 2 terminal regions:constant region : with constant amino acid sequence variable region with varying antibody specificity.

Immunoglobulin

A protein produced by lymphocytes in response to the entry of an antigen into the body.

Or Protein produced by the body in response to foreign antigens

I.IgG• Structure: Monomer• Molecular weight 160000• Make up 75-80% of serum antibodies• Location: distributed in intra vascular and extra vascular areas

• Half-life in serum: 23 days• Placental Transfer: Yes• Can be broken down by proteolytic enzymes

• Rate of synthesis 2g/day• Serum concentration 800-900mg/dl

Functions: • Opsonize (coating) the bacteria• Enhances phagocytosis• neutralizes bacterial toxins and viruses.

• Fix the complement with enhance bacteria killing.

II. IgM• Structure: Pentamer• Molecular weight 9-10 lac• Percentage serum antibodies: 8-10%• Serum concentration 30-130mg/dl• Rate of synthesis .1mg/dl• Location: restricted to blood because of large molecular weight and size

• More effective then IgG• Half-life in serum: 5 days• Placental Transfer: No

Functions:• First antibodies produced during an infection.

• Produce in primary response to an antigen.

• Fixes the complement

III. IgA• Structure: Dimer• Percentage serum antibodies: 15-20%• Serum concentration 50-190 mg/dl• Rate of synthesis 1.5 mg/day• Location: Secretions (tears, saliva, intestine, milk), blood and lymph.

• Half-life in serum: 6 days• Placental Transfer: No

Functions• Localized protection of mucosal surfaces. It prevents the attachment of bacteria and viruses on the mucous membrane.

IV. IgD• Structure: Monomer• Percentage serum antibodies: 1.0%• Rate of synthesis .02g/day • Serum concentration .02mg/dl• Location: B-cell surface• Half-life in serum: 2 days• Placental Transfer: No• Known Functions: In serum function is unknown.

V. IgE• Structure: Monomer• Percentage serum antibodies: 0.005%• Rate of synthesis is unknown • Serum concentration is .05mg/dl• Location: Bound to mast cells and basophils throughout body.

• Half-life in serum: 2 days• Placental Transfer: No

Functions:Mediate immediate hypersensitivity by causing release of chemical mediators from mast cells and basophils upon exposure to an Allergens.

Bacteria

Antibody

B cell

Stages of Phagocytosis1. Chemotaxis: Phagocytes are chemically attracted to site of infection.2. Adherence: Phagocyte plasma membrane attaches to surface of pathogen or foreign material.

Adherence can be inhibited by capsules (S. pneumoniae) or M protein (S. pyogenes).

Opsonization: Coating process with opsonins that facilitates attachment. Opsonins include antibodies and complement

proteins.

Phagocytes are Attracted to Site of Infection by Chemotaxis

Stages of Phagocytosis (Continued) 3. Ingestion: Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called phagosome.4. Digestion: Inside the cell, phagosome fuses with lysosome to form a phagolysosome.

Lysosomal enzymes kill most bacteria within 30 minutes and include:

Lysozyme: Destroys cell wall peptidoglycan Lipases and Proteases RNAses and DNAses

After digestion, residual body with undigestable material is discharged.

Process of Phagocytosis

Antimicrobial Substances: I. Complement System: Large group of serum

proteins that participate in the lysis of foreign cells, inflammation, and phagocytosis.

Two mechanisms of complement activation:1. Classical Pathway: Initiated by an immune

reaction of antibodies.2. Alternative Pathway: Initiated by direct

interaction of complement proteins with microbial polysaccharides.

Both pathways cleave a complement protein called C3, which triggers a series of events.

Classical Complement Pathway is Triggered by Antibodies Binding to Foreign Cells

Both Classical and Alternative Complement Pathways Trigger the Cleavage of C3

Consequences of Complement Activation: 1. Cytolysis: Due to the formation of a membrane attack complex (MAC) which produces lesions in microbial membranes.2. Inflammation: Complement components (C3a) trigger the release of histamine, which increases vascular permeability.3. Opsonization: Complement components (C3b) bind to microbial surface and promote phagocytosis.4. Inactivation of Complement: Regulatory proteins limit damage to host cells that may be caused by complement.

5. Agglutination:The complement products make the surface of the invading organism sticky causing adherence of the cells which promote agglutination.

6. Neutralization of virus:The complement enzyme and product attack on the virus and change its virulence factor.

7. Activation of mast cells and basophiles:C3a C4a C5a activate mast cells and basophile which release of histamine, heparin and other mediators which causes vasodilatation , increase blood vessel permeability and emigration of WBCs.

Interferons: Antiviral proteins that interfere with viral multiplication.

Small proteins (15,000 to 30,000 kDa) Heat stable and resistant to low pH Important in acute and short term infections. Have no effect on infected cells. Host specific, but not virus specific.

Interferon alpha and beta: Produced by virus infected cells and diffuse to neighboring cells. Cause uninfected cells to produce antiviral proteins (AVPs).Interferon gamma: Produced by lymphocytes. Causes neutrophils to kill bacteria.

Interleukins:• interleukins are a group of cytokines that were

first seen to be expressed by white blood cells (leukocytes).

• The term interleukin derives from (inter-) "as a means of communication", and (-leukin) "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes".

• The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency.

• The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells.

• They promote the development and differentiation of T, B, and hematopoietic cells

Interleukin 1:Source: macrophages, B cells, monocytes, dendritic cells.Target cells: T helper cells, B cells, NK cellsFunction:inflammation, small amounts induce acute phase reaction, large amounts induce fever

Interleukin 2:Source: Th1-cellsTarget cells: Activated T cells and B cells, NK cells,macrophages,oligodendrocytesFunction:Stimulates growth and differentiation of T cell response. Can be used in immunotherapy to treat cancer or suppressed for transplant patients

Interleukin 3:Source: activated T helper cells, mast cells, NK cells,Target cells: hematopoietic stem cellsFunction:Differentiation and proliferation of myeloid progenitor cells  to e.g. erythrocytes, granulocytes

Interleukin 4:Source: Th2 cells, memory CD4+ cells, mast cells,macrophagesTarget cells:activated B cells, T cells endotheliumFunction:proliferation and differentiation, IgG1 and IgE synthesis. Important role in allergic response (IgE)

Interleukin 5:Source: Th2 cells, mast cells,eosinophilsTarget cells: eosinophils, B cells Function:Differentiation, IgA production

Interleukin 6:Source: macrophages, Th2 cells, B cells, astrocytes, endotheliumTarget cells: activated B cells, plasma cells, hematopoietic stem cells. Function:• Differentiation into plasma cells• Antibody secretion• Differentiation